Selective GPR84 Antagonist
Selective G-protein coupled receptor 84 (GPR84) Antagonist
GPR84 is a pro-inflammatory target primarily expressed on cells associated with the immune system and its expression levels increase significantly during periods of inflammatory stress. Inhibition of GPR84 can inhibit neutrophil and macrophage migration and reduce cytokine release.
However, GPR84 expression is not restricted to cells in the immune system; it is also expressed in tissues such as the brain, heart, muscle, colon, kidney, liver, intestine, adipose and lung. Through its role in inflammation, GPR84 may be a mediator of the relationship between inflammation, obesity and diabetes. Rodent models suggest that GPR84 expression is up-regulated in adipocytes in response to TNF-α released from infiltrating macrophages, and that this in turn can lead to a down-regulation in adiponectin expression in adipocytes. Adiponectin is known to have anti-diabetic, anti-inflammatory, and anti-atherogenic effects, and it also functions as an insulin sensitizer.
Our GPR84 antagonist program
In addition to our experienced in-house medicinal chemistry group, we have a strong understanding and well-established, in-house expertise in GPR84 biology. Our prior research has shown that GPR84-deficient mice develop reduced fibrosis in a model of kidney fibrosis (adenine-induced chronic kidney disease). We have also shown that GPR84 mRNA is overexpressed in various acute and chronic kidney models such as 5/6-nephrectomy (Nx)-induced chronic kidney disease, doxorubicin (DOX)-induced nephropathy and in adenine-induced tubulointerstitial injury.
Our GPR84 antagonist program is currently at the pre-clinical stage.
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- A Newly Discovered Antifibrotic Pathway Regulated by Two Fatty Acid Receptors GPR40 and GPR84
- Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction
- Therapeutic validation of an orphan G protein-coupled receptor: The case of GPR84
- An expressed sequence tag (EST) data mining strategy succeeding in the discovery of new G-protein coupled receptors
- Inflammatory changes in adipose tissue enhance expression of GPR84, a medium-chain fatty acid receptor: TNFα enhances GPR84 expression in adipocytes
- Medium-chain Fatty Acids as Ligands for Orphan G Protein-coupled Receptor GPR84
- Activation of the Immune-Metabolic Receptor GPR84 Enhances Inflammation and Phagocytosis in Macrophages
- Pharmacology of Free Fatty Acid Receptors and Their Allosteric Modulators